rs3833748

Variant names:

• chr11-72190417-TC-T
• rs3833748
• ENST00000393679.5:c.-228delC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000393679.5(FOLR1):​c.-228delC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 152,212 control chromosomes in the GnomAD database, including 208 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (208 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOLR1 ENST00000393679.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 5 publications found

Genes affected

FOLR1 (HGNC:3791): (folate receptor alpha) The protein encoded by this gene is a member of the folate receptor family. Members of this gene family bind folic acid and its reduced derivatives, and transport 5-methyltetrahydrofolate into cells. This gene product is a secreted protein that either anchors to membranes via a glycosyl-phosphatidylinositol linkage or exists in a soluble form. Mutations in this gene have been associated with neurodegeneration due to cerebral folate transport deficiency. Due to the presence of two promoters, multiple transcription start sites, and alternative splicing, multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Oct 2009]

FOLR1 Gene-Disease associations (from GenCC):

• neurodegenerative syndrome due to cerebral folate transport deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ENSG00000204971 (HGNC:58347):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOLR1	NM_000802.3	c.-9+491delC		intron_variant	Intron 1 of 4		NP_000793.1
FOLR1	NM_016724.3	c.-74-154delC		intron_variant	Intron 1 of 5		NP_057936.1
FOLR1	NM_016725.3	c.-9+663delC		intron_variant	Intron 1 of 4		NP_057937.1
FOLR1-AS1	NR_199595.1	n.419+8095delG		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOLR1	ENST00000393679.5	c.-228delC		5_prime_UTR_variant	Exon 1 of 5	1		ENSP00000377284.1
FOLR1	ENST00000312293.9	c.-9+663delC		intron_variant	Intron 1 of 4	1		ENSP00000308137.4
FOLR1	ENST00000393681.6	c.-74-154delC		intron_variant	Intron 1 of 5	1		ENSP00000377286.2

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5802 AN: 152094 Hom.: 206 Cov.: 32

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0788

Gnomad SAS AF: 0.0648

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00961

Gnomad OTH AF: 0.0311

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0382 AC: 5809 AN: 152212 Hom.: 208 Cov.: 32 AF XY: 0.0392 AC XY: 2917 AN XY: 74434

African (AFR) AF: 0.0922 AC: 3828 AN: 41506

American (AMR) AF: 0.0196 AC: 300 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3472

East Asian (EAS) AF: 0.0788 AC: 408 AN: 5176

South Asian (SAS) AF: 0.0647 AC: 312 AN: 4824

European-Finnish (FIN) AF: 0.0134 AC: 142 AN: 10616

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00963 AC: 655 AN: 68018

Other (OTH) AF: 0.0303 AC: 64 AN: 2112

Alfa AF: 0.0263 Hom.: 8

Bravo AF: 0.0408

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.39
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3833748; hg19: chr11-71901461;